Gout
In medicine, gout is a "hereditary metabolic disorder characterized by recurrent acute arthritis, hyperuricemia and deposition of sodium urate in and around the joints, sometimes with formation of uric acid calculi."[1]
Treatment
Clinical practice guidelines address treatment.[2] However, trials comparing glucocorticoids and non-steroidal anti-inflammatory agents (NSAIDs) were not published till after the guidelines.
Ice packs, applied for 30 minutes 4 times per day, can help according to a randomized controlled trial without allocation concealment.[3] In this trial, ice reduced the visual pain analog score by an additional 33 mm beyond the reduction provided by a combination of glucocorticoids and colchicine.
Regarding medications, if there are no mitigating factors in choosing a drug, steroids, non-steroidal anti-inflammatory agents (NSAIDs), and colchicine all work; however, colchicine consistently causes drug toxicity. While combining steroids with NSAIDs increased the risk for gastrointestinal drug toxicity[4], colchicine can be combined with steroids and possibly with NSAIDs that are not metabolized by the CYP3A4 isoenzyme of cytochrome P-450.
Non-steroidal anti-inflammatory agents
Non-steroidal anti-inflammatory agents (NSAIDs) are better than placebo according to a randomized controlled trial.[5] According to a summary of this trial, "the knee was affected in 14 cases and the great toe in only two cases. After 24 h, 67% of tenoxicam group had ≥50% reduction in pain compared with 26% of placebo group (P<0.05). However, at the end of the treatment (4 days), there was no significant difference between the groups."[6]
Glucocorticoids
| Patients | Interventions | Results | ||
|---|---|---|---|---|
| Steroid | NSAID | |||
| Janssens et al 2008[7] | 120 total patients with uric acid crystals on arthrocentesis | Prednisolone 35 mg once daily for 5 days | Naproxen 500 mg twice daily for 5 days | NSAID trended better (88% versus 80% response; p=0.3) No differences in rates of drug toxicity. |
| Man et al 2007[8] | 90 total patients with clinical diagnosis of gout† | Initially prednisolone 30 mg Followed by prednisolone 30 mg daily for 5 days and as needed acetaminophen |
Initially diclofenac 75 mg with indomethacin 50 mg Followed by indomethacin 50 mg every 8 hrs for 2 days then 25 mg every 8 hrs for 3 days and as needed acetaminophen. |
Steroids faster reduction in pain. Steroids used more acetaminophen. More adverse effects from indomethacin. Indomethacin trended to more relapses at 2 weeks (11% vs 17%). |
| Notes: † Clinical diagnosis of gout was "pain and warmth in a joint, and presented within 3 days of the onset of pain and also had 1 or more of the following: metatarsal-phalangeal joint involvement; knee or ankle joint involvement and aspirate containing crystals; or typical gouty arthritis, with either gouty tophi present or previous joint aspiration confirming the diagnosis of gout." Seven patients allowed arthrocentesis and all were positive for gout. | ||||
Randomized controlled trials find similar benefit from non-steroidal anti-inflammatory agents and oral glucocorticoids. In the first trial the reduction in visual analog scale after 5 days was 44.7 with prednisolone and 46.0 with naproxen.[8] Less adverse drug reactions occurred in the glucocorticoids group; however, the NSAID group received a high dose (50 mg every 8 hours for 2 days, followed by 25 mg every 8 hours for 3 days)[9].
In the second randomized controlled trial statistically equal effect resulted from prednisolone 35 mg orally per day or naproxen 500 mg orally twice per day; however there was an insignificant 8% improvement in the NSAID group.[7] There were no significant differences in drug toxicity.
Colchicine
Colchicine is better than placebo according to a systematic review by the Cochrane Collaboration[10] that found a single randomized controlled trial[11]. In this study, colchicine 1 mg orally, followed by 0.5 mg every two hours led to a 50% reduction in pain in about 70% of patients compared to about 35% of patients who received placebo. However, all patients had drug toxicity from colchicine and in 90% of the patients toxicity occurred before 50% reduction in pain.
To avoid drug toxicity, lower doses of colchicine (0.6 per day) have been used in combination with glucocorticoids.[3] The UK National Library for Health recommends 0.5 mg two to four times a day.[12]
Prognosis
Acute flares
Without treatment, one third of flares improve within 2 days.[11]
Prevention
Diet
Avoiding products with high fructose such as sugary soft drinks (sweetened with high fructose corn syrup), and other high-fructose products, such as fruit juice, apples, and oranges may help.[13]
Medications
Xanthine oxidase inhibitors
Allopurinol can reduce frequency of attacks. However, when allopurinol is started:
- Allopurinol should be delayed for 1-2 weeks after a flare has resolved
- Colchicine 0.6 mg twice daily should also be used to prevent a flare. In a randomized controlled trial, co-treatment with colchicine 0.6 mg twice daily while allopurinol was tapered up from 100 mg/day until 3 months after the serum urate concentration < 6.5 mg/dl, reduced flares of gout from 77% in the placebo broup to 33% with colchicine prophylaxis. Most of these patients had tophi.[14]
Allopurinol should be increased as possible to achieve a goal serum urate of <6 mg/dl (360 micromoles/liter).[15]
Febuxostat, a non-purine inhibitor, is equally effective as allopurinol when compared in a randomized controlled trial.[16]
Uricosuric agents
Famous persons with gout
Holy Roman Emperor Charles V had gout[17]and Theodore Roosevelt may have had gout[18].
References
- ↑ Anonymous (2024), Gout (English). Medical Subject Headings. U.S. National Library of Medicine.
- ↑ Zhang W, Doherty M, Bardin T, et al (October 2006). "EULAR evidence based recommendations for gout. Part II: Management. Report of a task force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT)". Ann. Rheum. Dis. 65 (10): 1312–24. DOI:10.1136/ard.2006.055269. PMID 16707532. Research Blogging.
- ↑ 3.0 3.1 Schlesinger N, Detry MA, Holland BK, et al (2002). "Local ice therapy during bouts of acute gouty arthritis". J. Rheumatol. 29 (2): 331–4. PMID 11838852. [e]
Cite error: Invalid
<ref>tag; name "pmid11838852" defined multiple times with different content - ↑ Fries JF, Williams CA, Bloch DA, Michel BA (September 1991). "Nonsteroidal anti-inflammatory drug-associated gastropathy: incidence and risk factor models". Am. J. Med. 91 (3): 213–22. PMID 1892140. [e]
- ↑ García de la Torre, Ignacio. (1987) Estudio doble-ciego paralelo, comparativo con tenoxicam vs placebo en artritis gotosa aguda (A comparative, double-blind, parallel study with tenoxicam vs placebo in acute gouty arthritis). Invet Med Int '14:'92–7 [Abstract in Spanish]
- ↑ Sutaria S, Katbamna R, Underwood M (November 2006). "Effectiveness of interventions for the treatment of acute and prevention of recurrent gout--a systematic review". Rheumatology (Oxford) 45 (11): 1422–31. DOI:10.1093/rheumatology/kel071. PMID 16632483. Research Blogging.
- ↑ 7.0 7.1 Janssens HJ, Janssen M, van de Lisdonk EH, van Riel PL, van Weel C (May 2008). "Use of oral prednisolone or naproxen for the treatment of gout arthritis: a double-blind, randomised equivalence trial". Lancet 371 (9627): 1854–60. DOI:10.1016/S0140-6736(08)60799-0. PMID 18514729. Research Blogging.
- ↑ 8.0 8.1 Man CY, Cheung IT, Cameron PA, Rainer TH (2007). "Comparison of oral prednisolone/paracetamol and oral indomethacin/paracetamol combination therapy in the treatment of acute goutlike arthritis: a double-blind, randomized, controlled trial". Annals of emergency medicine 49 (5): 670–7. DOI:10.1016/j.annemergmed.2006.11.014. PMID 17276548. Research Blogging.
- ↑ Henry D, Lim LL, Garcia Rodriguez LA, et al (June 1996). "Variability in risk of gastrointestinal complications with individual non-steroidal anti-inflammatory drugs: results of a collaborative meta-analysis". BMJ 312 (7046): 1563–6. PMID 8664664. PMC 2351326. [e]
- ↑ Schlesinger N, Schumacher R, Catton M, Maxwell L (2006). "Colchicine for acute gout". Cochrane Database Syst Rev (4): CD006190. DOI:10.1002/14651858.CD006190. PMID 17054279. Research Blogging.
- ↑ 11.0 11.1 Ahern MJ, Reid C, Gordon TP, McCredie M, Brooks PM, Jones M (June 1987). "Does colchicine work? The results of the first controlled study in acute gout". Aust N Z J Med 17 (3): 301–4. DOI:10.1111/j.1445-5994.1987.tb01232.x. PMID 3314832. Research Blogging.
Summary at Bandolier Cite error: Invalid
<ref>tag; name "pmid3314832" defined multiple times with different content - ↑ CKS (2007) Gout - Mangement (Topic Review). Clinical Knowledge Summaries. http://cks.library.nhs.uk/gout/management [Accessed: Date]
- ↑ Hyon K Choi and Gary Curhan, “Soft drinks, fructose consumption, and the risk of gout in men: prospective cohort study,” BMJ (January 31, 2008): bmj.39449.819271.BE.
- ↑ Borstad GC, Bryant LR, Abel MP, Scroggie DA, Harris MD, Alloway JA (2004). "Colchicine for prophylaxis of acute flares when initiating allopurinol for chronic gouty arthritis". J. Rheumatol. 31 (12): 2429–32. PMID 15570646. [e]
- ↑ Perez-Ruiz F, Lioté F (2007). "Lowering serum uric acid levels: What is the optimal target for improving clinical outcomes in gout?". Arthritis Rheum. 57 (7): 1324–8. DOI:10.1002/art.23007. PMID 17907217. Research Blogging.
- ↑ Becker MA, Schumacher HR Jr, Wortmann RL, MacDonald PA, Eustace D, Palo WA, Streit J, Joseph-Ridge N.Febuxostat compared with allopurinol in patients with hyperuricemia and gout.N Engl J Med. 2005 Dec 8;353(23):2450-61. PMID 16339094
- ↑ Ordi J, Alonso PL, de Zulueta J, et al (August 2006). "The severe gout of Holy Roman Emperor Charles V". N. Engl. J. Med. 355 (5): 516–20. DOI:10.1056/NEJMon060780. PMID 16885558. Research Blogging.
- ↑ Pinals RS (February 2008). "Theodore Roosevelt's inflammatory rheumatism". J Clin Rheumatol 14 (1): 41–4. DOI:10.1097/RHU.0b013e3181639ad0. PMID 18431099. Research Blogging.